The overall objectives of the proposed research are to: 1) characterize the biochemical and molecular genetics of human acid sphingomyelinase, the lysosomal hydrolase deficient in the neuronopathic (Type A) and non-neuronopathic (Type B) forms of Niemann-Pick disease (NPD), and 2) use the murine model of NPD for the development and evaluation of enzyme replacement and somatic gene transfer strategies for the treatment of this lysosomal storage disease.